Dataset Information

Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis.

ABSTRACT: COVID-19 (coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the pathophysiology of this virus is complex and largely unknown, we employed a network-biology-fueled approach and integrated transcriptome data pertaining to lung epithelial cells with human interactome to generate Calu-3-specific human-SARS-CoV-2 interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 targets central nodes of the host-viral network, which participate in core functional pathways. Network centrality analyses discover 33 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation, and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host-modifying responses and cytokine storm. Overall, our network-centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into the pathogenicity of SARS-CoV-2 that may help foster effective therapeutic design.

SUBMITTER: Kumar N

PROVIDER: S-EPMC7468341 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis.

Kumar Nilesh N Mishra Bharat B Mehmood Adeel A Mohammad Athar M Shahid Mukhtar

iScience 20200903 9

COVID-19 (coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the pathophysiology of this virus is complex and largely unknown, we employed a network-biology-fueled approach and integrated transcriptome data pertaining to lung epithelial cells with human interactome to generate Calu-3-specific human-SARS-CoV-2 interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 targets centr ...[more]

PMID: 32895641

Similar Datasets

Project description:The world has recently been plagued by a new coronavirus infection called SARS-CoV-2. This virus may lead to severe acute respiratory syndrome followed by multiple organ failure. SARS-CoV-2 has approximately 80-90% genetic similarity to SARS-CoV. Given the limited omics data available for host response to the viruses (more limited data for SARS-CoV-2), we attempted to unveil the crucial molecular mechanisms underlying the SARS-CoV-2 pathogenesis by comparing its regulatory network motifs with SARS-CoV. We also attempted to identify the non-shared crucial molecules and their functions to predict the specific mechanisms for each infection and the processes responsible for their different manifestations. Deciphering the crucial shared and non-shared mechanisms at the molecular level and signaling pathways underlying both diseases may help shed light on their pathogenesis and pave the way for other new drug repurposing against COVID-19. We constructed the GRNs for host response to SARS-CoV and SARS-CoV-2 pathogens (in vitro) and identified the significant 3-node regulatory motifs by analyzing them topologically and functionally. We attempted to identify the shared and non-shared regulatory elements and signaling pathways between their host responses. Interestingly, our findings indicated that NFKB1, JUN, STAT1, FOS, KLF4, and EGR1 were the critical shared TFs between motif-related subnetworks in both SARS and COVID-1, which are considered genes with specific functions in the immune response. Enrichment analysis revealed that the NOD-like receptor signaling, TNF signaling, and influenza A pathway were among the first significant pathways shared between SARS and COVID-19 up-regulated DEGs networks, and the term "metabolic pathways" (hsa01100) among the down-regulated DEGs networks. WEE1, PMAIP1, and TSC22D2 were identified as the top three hubs specific to SARS. However, MYPN, SPRY4, and APOL6 were the tops specific to COVID-19 in vitro. The term "Complement and coagulation cascades" pathway was identified as the first top non-shared pathway for COVID-19 and the MAPK signaling pathway for SARS. We used the identified crucial DEGs to construct a drug-gene interaction network to propose some drug candidates. Zinc chloride, Fostamatinib, Copper, Tirofiban, Tretinoin, and Levocarnitine were the six drugs with higher scores in our drug-gene network analysis.Supplementary informationThe online version contains supplementary material available at 10.1007/s13205-023-03518-x.

Project description:Accumulating data suggest that chronic neuroinflammation-mediated neurodegeneration is a significant contributing factor for progressive neuronal and glial cell death in age-related neurodegenerative pathology. Furthermore, it could be encountered as long-term consequences in some viral infections, including post-COVID-19 Parkinsonism-related chronic sequelae. The current systematic review is focused on a recent question aroused during the pandemic's successive waves: are there post-SARS-CoV-2 immune-mediated reactions responsible for promoting neurodegeneration? Does the host's dysregulated immune counter-offensive contribute to the pathogenesis of neurodegenerative diseases, emerging as Parkinson's disease, in a complex interrelation between genetic and epigenetic risk factors? A synthetic and systematic literature review was accomplished based on the "Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses" (PRISMA) methodology, including registration on the specific online platform: International prospective register of systematic reviews-PROSPERO, no. 312183. Initially, 1894 articles were detected. After fulfilling the five steps of the selection methodology, 104 papers were selected for this synthetic review. Documentation was enhanced with a supplementary 47 bibliographic resources identified in the literature within a non-standardized search connected to the subject. As a final step of the PRISMA method, we have fulfilled a Population-Intervention-Comparison-Outcome-Time (PICOT)/Population-Intervention-Comparison-Outcome-Study type (PICOS)-based metanalysis of clinical trials identified as connected to our search, targeting the outcomes of rehabilitative kinesitherapeutic interventions compared to clinical approaches lacking such kind of treatment. Accordingly, we identified 10 clinical trials related to our article. The multi/interdisciplinary conventional therapy of Parkinson's disease and non-conventional multitarget approach to an integrative treatment was briefly analyzed. This article synthesizes the current findings on the pathogenic interference between the dysregulated complex mechanisms involved in aging, neuroinflammation, and neurodegeneration, focusing on Parkinson's disease and the acute and chronic repercussions of COVID-19. Time will tell whether COVID-19 neuroinflammatory events could trigger long-term neurodegenerative effects and contribute to the worsening and/or explosion of new cases of PD. The extent of the interrelated neuropathogenic phenomenon remains obscure, so further clinical observations and prospective longitudinal cohort studies are needed.

Dataset Information

Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis.

Publications

Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets